Travel-Related Shigellosis in Quebec, Canada: An Analysis of Risk Factors

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1 I S T M 304 ORIGINAL ARTICLE Travel-Related Shigellosis in Quebec, Canada: An Analysis of Risk Factors Stéphane Trépanier, MD, FRCPC, Yen-Giang Bui, MD, DTMH, Manon Blackburn, MD, FRCPC, François Milord, MD, MSc, Éric Levac, MD, and Suzanne Gagnon, MD, MA Public Health Department, CSSS Manicouagan, Baie-Comeau, Canada; Quebec Advisory Committee on Travel Health, Institut national de santé publique du Québec, Québec, Canada; Public Health Department, CSSS Champlain-Charles-Lemoyne, Longueuil, Canada; Community Health Department Université de Sherbrooke, Sherbrooke, Canada DOI: /jtm Background. Travel-related shigellosis is not well documented in Canada although it is frequently acquired abroad and can cause severe disease. Objectives. To describe the epidemiology of travel-related cases of shigellosis for Quebec (Canada) and to identify high-risk groups of travelers. Method and Data Sources. We performed a random sampling of 335 shigellosis cases (from a total of 760 cases) reported in the provincial database of reportable diseases from January 1, 2004, to December 31, Each case was analyzed according to information available in the epidemiology questionnaire. Total number of trips by region from Statistics Canada was used as denominator to estimate the risk according to region of travel. Results. Annually, between 43 and 54% of the shigellosis cases were reported in travelers, 45% of whom were aged between 20 and 44 years. Children under 11 years accounted for nearly 16% of cases, but represent only 4% of travelers. Most cases in travelers were serogroups Shigella sonnei (50%) or Shigella flexneri (45%). Almost 31% of cases were reported between January and March. The majority (64%) were acquired in Central America, Mexico, or the Caribbean. However, the Indian subcontinent, Africa, and South America had the highest ratio of number of cases per number of trips. Tourists represented 76% of the cases; 62% of them had traveled for <2 weeks. At least 15% of cases among travelers were hospitalized. Conclusions. In Quebec, travel-related cases of shigellosis represent a large burden of total cases. Short-term travelers are at risk, as well as young children. The majority of cases occur in the winter months, corresponding to the peak of travel to sunshine destinations. Continuous efforts should be made to encourage all travelers to seek pre-travel care, and to inform primary care practitioners of health risks faced by their patients abroad, even for those going to resorts. Shigellosis is the most common cause of dysentery worldwide. It is estimated that between 80 and 165 million cases occur annually, with up to 1,100,000 deaths. 1,2 In the United States, around 14,000 cases are Preliminary results were presented at the 7th European Congress on Tropical Medicine and International Health, Barcelona, Spain, October 3 6, Corresponding Author: Yen-Giang Bui, MD, DTMH, Programme maladies transmissibles, Direction de santé publique, Agence de la santé et des services sociaux de la Montérégie, 1255, rue Beauregard, Longueuil, QC, Canada J4K 2M3. yen.bui.agence16@ssss.gouv.qc.ca reported each year. 3 The epidemiology of shigellosis in travelers is rarely documented in Canada, although it represents 7% to 9% of cases of travelers diarrhea when the pathogen is known. 4,5 There are four serogroups of Shigella, the rod-shaped bacillus that causes shigellosis, and the only significant reservoir is human. Shigella sonnei is the most frequent serogroup found in developed countries such as the United States and Canada. The second, Shigella flexneri, is endemic in most low-income countries. Shigella boydii is prevalent mainly in the Indian subcontinent. Fatality rate can reach 20% with Shigella dysenteriae, present also in low-income countries, but it is usually much lower for other serogroups. 1,2, International Society of Travel Medicine, Journal of Travel Medicine 2014; Volume 21 (Issue 5):

2 Travel-Related Shigellosis 305 Shigellae are characterized by a very low infecting dose, from 10 to 100 organisms. Transmission occurs via the fecal oral route, through contaminated food or water. The incubation period is short, varying between 12 and 96 hours, and the disease lasts usually from 5 to 7 days. Symptoms include fever, bloody diarrhea, nausea, vomiting, and abdominal cramps. The transmission period extends from acute infection until the organism is no longer present in feces, usually about 4 weeks after illness. 6 Ciprofloxacin is the antibiotic of choice and shortens the infectious period to a few days. 1,4,6,7 Resistance to quinolones is a growing problem, 2,7 10 and other antibiotics such as ceftriaxone and azithromycin can be prescribed as second choices, 1,6 although resistance to azithromycin has been recently described in Bangladesh. 11 Young age (2 4 years) and lack of hygiene are risk factors for the acquisition of shigellosis in travelers to developing countries. 12 Presently, the only preventive measures consist of enteric precautions and chemoprophylaxis for special groups of travelers. 3,4,12 Vaccines are in development, but challenges remain in discovering a vaccine that covers the different serogroups and serotypes of Shigella. 3,13 15 To identify high-risk groups of travelers and destinations at risk for the acquisition of shigellosis and to target preventive measures, we studied the epidemiology of travel-related shigellosis in Canadian travelers (Quebec) between 2004 and Data and Methodology The results presented here are extracted from a cross-sectional study of cases of shigellosis, malaria, typhoid, and hepatitis A reported in travelers between 2004 and 2007 in the province of Quebec. 16,17 It is the second most populous province of Canada, with a population of close to 8 million inhabitants. Quebec is divided into 18 health regions, with a Department of Public Health in each region mandated to carry out surveillance of infectious diseases. In Quebec, shigellosis is a mandatory reportable disease by laboratories and all cases with a positive culture must be reported to the regional Department of Public Health of the patient s residence, which then enters the information into the provincial reportable diseases database. This database contains cases of shigellosis, demographic information, reporting date, serogroup, and whether the case was travel-related or not. Reporting of antibiotic susceptibility is not mandatory for shigellosis. Each reported case generally undergoes an epidemiological investigation by the regional public health department. A case is considered to be travel-related if the patient reported a history of travel outside Quebec during the exposure period, ie, from 4 (S. sonnei/flexneri/boydii) to 7days(S. dysenteriae) before the beginning of symptoms and up until 12 hours before the beginning of symptoms. The epidemiology questionnaire provides additional information such as destination, duration, and type of travel. In this study, we defined travel-related cases as all cases with a history of travel outside Canada or the United States. We excluded cases in recent immigrants and adoptees. Travelers were further categorized into tourists going to resorts, visiting friends and relatives (VFRs), and work/study/volunteering, as noted in the questionnaires. Between January 1, 2004 and December 31, 2007, 760 cases of shigellosis were reported in the provincial database. Since the whole study comprised three other diseases (hepatitis A, malaria, and typhoid) and manpower was limited, a sample of 335 cases of shigellosis was chosen by randomized sampling. An initial size of 255 was estimated considering a power of 80%, with an α level of 0.05; since the frequency of the main risk factors was unknown, we considered a prevalence of 50%, with a precision of 5% around the estimate. Expecting that some epidemiology questionnaires would not be available for the study, we raised the sample size to 335 cases. For the purposes of this study, a denominalized copy of the questionnaire was requested from the regional Departments of Public Health for the 335 selected cases. We received a copy for 331 cases (98.5%). A pre-test form was used to extract pertinent and available data, such as age, gender, history of international travel, country visited, length and purpose of the trip, and the outcome of the episode. Descriptive analyses of these variables are presented and a computation of the risk of shigellosis associated with each world region is done. This analysis requires an estimate of the number of travelers. These numbers are not available in Quebec; so for the denominator we relied on estimation for the number of trips, which comes from surveys and counts of travels by Quebecers conducted at border crossings by Statistics Canada between 2004 and To minimize biases in terms of distribution and nonresponse in these surveys, Statistics Canada has developed different methods of adjustments and weighting. 19 The project was approved by the administrative and research ethics board of Charles-LeMoyne Hospital, Longueuil, Canada. Results Proportion of Cases Linked to Travels We received a total of 331 questionnaires. Information on history of travel was available in 300 questionnaires, and was missing in 31 questionnaires. In total, 149 cases were reported after an international trip (Figure 1). The proportion of travel-related cases varied from 43% to 54% annually, with an average of 49%. Serogroups of Shigella Information on serogroup was available for 139 travel-related cases. The two most frequent serogroups

3 306 Trépanier et al. Figure 3 Number of reported cases of shigellosis and ratio per 1,000,000 trips according to region of travel, Quebec, Canada, (N = 146). Figure 1 Number of reported cases of shigellosis according to a history of recent international travel, Quebec, Canada, (N = 300). We have estimated the ratio (R) of the number of cases over 1,000,000 trips to find the regions with highest risk. These regions were the Indian subcontinent, Africa, and South America. Few cases were reported in travelers returning from Asian countries other than the Indian subcontinent. Purpose and Duration of Travel Shigellosis occurred in all categories of travelers. We had information on the purpose of travel for 113 cases and on the trip duration for 139 cases. Tourists represented the most frequent category of travelers (76%) (Table 1). Most cases (62%) occurred on a trip of <2 weeks duration, with nearly 40% of those occurring on a trip of 1 to 7 days. Age Distribution Among travelers, 45% (68) of all cases were aged from 20 to 44 years and nearly 16% (24) were 11 years or younger (Figure 4). This younger age group represents 4% of all international travelers from Quebec. 18 Figure 2 Number of reported cases of shigellosis according to serogroup and history of recent international travel, Quebec, (N = 300). of Shigella in travelers are S. sonnei, accounting for 69 cases (50%) and S. flexneri, 63 cases (45%) (Figure 2). Cases of S. dysenteriae, usually more severe, appear to be quite rare in travelers from Quebec. Regions of the World Where the Infection Was Acquired The number of cases (n = 146) among travelers according to the region of travel is shown in Figure 3. Ninety three or 64% of the above visited Central America, Mexico, or the Caribbean. Furthermore, 45 cases (nearly 31%) were reported from January to March (results not shown). This correlates with the peak of travel to these popular destinations for Quebec travelers. Burden of Disease According to the epidemiology questionnaire, between 2004 and 2007, at least 15% of the travel-related cases of shigellosis were hospitalized for this infection, a rate similar to non-travel-related cases (18%). The majority of cases were either not hospitalized or the information was missing. No other data on complications is available. No related death was reported during the study period. Discussion Trip Duration and Type of Travel Shigellosis differs from other travel-acquired infections in that most cases occurred following short trips of <2 weeks, and in our study almost 40% following a trip of <7 days. Most cases are probably associated with tourists visiting resorts, which correlates with the fact that organized trips typically lasts for 1 or 2 weeks, and the fact that the peak of reported

4 Travel-Related Shigellosis 307 Table 1 Proportion of cases of shigellosis in travelers according to the purpose and the duration of travel, Quebec, Canada, N Proportion of cases (%) CI 95% Estimated proportion of trips taken by Quebec travelers (%) 18 Purpose of travel Tourism Work/study/volunteer Visiting friends and relatives Total Duration of travel 1 13 days* days Total *39.2% of cases in travelers occurred on a trip of <8days. such as those undertaken by travelers VFRs and volunteers, an episode of travelers diarrhea (either caused by shigellosis or other pathogens) gets resolved before the return, and thus escaped our surveillance. One element favoring this hypothesis is the short incubation period of shigellosis (12 96 hours) compared to hepatitis A for example (15 50 days). 1,3 Another reason may be that longer-term travelers may be better prepared, or possibly have developed immunity to local pathogens. 20 Figure 4 Proportion of reported cases of shigellosis according to age group and history of recent international travel, Quebec, Canada, (N = 300). cases (January March) corresponds to the peak of winter travel season for Quebec travelers. Perhaps travelers on short business trips are also at risk, but our data could not determine this. Our data on travel-related shigellosis mirrors data on enteric illnesses from other studies. A GeoSentinel study reported that travel for reasons of tourism demonstrated the highest risk, and that short-term travelers (<28 days) were more likely to present with a gastrointestinal illness than longer-term travelers (>28 days). 20 Another study reported that Latin America and the Caribbean region accounted for most travel-associated enteric infections diagnosed in the United States, although travel to Africa carries the greatest risk, followed by Asia. 21 Some factors could put tourists at risk. One may suppose that tourists, having been vaccinated against hepatitis A, might think they are protected against other enteric infections, and thus take fewer precautions. Unfortunately, our data do not allow for confirmation of this hypothesis. It is also possible that on longer trips Age Shigellosis is a disease that affects children in particular 2,3,22 24 as much in travelers as in nontravelers. The median age of our cases is 33 years and is probably influenced by the important proportion of adults among travelers. Nevertheless, children appear to be more at risk, when we compare the proportion of cases in those below 11 years to the proportion of Quebec travelers in the same age group. This age group also represents the most important group of cases of shigellosis acquired in Quebec. Real Burden of Travel-Related Shigellosis An underestimation of the real burden of shigellosis is very probable for many reasons. Since our surveillance is laboratory-dependent, mildly symptomatic cases and cases for which a stool culture was not submitted could not be identified. Also, we cannot discount the importance of secondary cases of shigellosis. Some cases could have been associated with a sick traveler but not accounted for in the burden of and in the incidence of travel-related cases. With available data, it was not possible to identify cases secondary to an index case that was travel-related. We were not able to link the provincial reportable diseases database with the provincial database on hospitalization, because it would require special authorization. Moreover, this database is mainly collected for administrative purposes, and does not contain much clinical information. Fortunately, the epidemiology

5 308 Trépanier et al. questionnaires provided information on hospital admission in reported cases. Since a hospitalized case would probably have a laboratory confirmation of shigellosis and would have been included in the reportable disease database, we do not think that the database on hospital admission would have provided many more cases. A study from 1995 to 2004 appears to confirm this. It estimated that a mean of 108 cases of shigellosis were hospitalized each year in Canada, which represents 13% of the 813 cases reported each year, 25,26 a proportion similar to what we observed (15 18%). Principal Regions of Acquisition of the Disease The ratio of the number of cases to the number of travelers allows us to estimate the potential risk of a geographic region, notwithstanding its popularity. Therefore, a traveler to either the Indian subcontinent or Africa is more at risk than a traveler to Mexico. In this, our results are similar to those from a study by Ekdahl and Andersson. 22 Still, we should not discount the importance of common tourist destinations where the majority of our cases occurred, reflecting the large number of tourists traveling to those destinations. The number of cases reported in returning travelers from Asia is lower than expected. According to one study, Shigella infections from Asia should represent 4% to 7% of cases of travelers diarrhea. 27 Serogroups of Shigella The small proportion of cases of S. dysenteriae and S. boydii observed in our study concurs with a Swedish study from 2005, in which a proportion of 3% and 5% have been found respectively for those two serogroups. 22 According to Kotloff and colleagues, in developed countries, 1% of reported cases are S. dysenteriae and 2% are S. boydii. 2 Typically, S. sonnei is found more frequently in industrialized countries and S. flexneri more commonly in low-income countries. 2,3,28 A preponderance of S. sonnei in travelers has also been noted in the Swedish study. 22 Limits and Strengths The provincial database on reportable diseases ensures that all cases of reported shigellosis were eligible to be included in the study. However, this study does not describe all cases, since clinical cases that were not confirmed are not included in the data source. We can surmise that cases related to travel would prompt more attention from clinicians, and thus lead to more diagnosis and reporting compared to non-travel-related cases. If this is true, the proportion of cases related to travel may be overestimated in this study. As for any sample, cases included in this study are susceptible to a selection bias, but random sampling should reduce that risk. Information relative to risk factors was extracted from epidemiology questionnaires, some with missing data. This could have resulted in variations in observed proportions, but in our opinion it is not probable that an important bias could have been introduced, since information on travel was missing in <10% of cases. There was a lot of missing data on hospitalization in our study and that may have caused an underestimation of the real morbidity of shigellosis, although another recent study on hospitalizations for gastrointestinal illnesses in Canada showed similar results. 25 Antibiotic resistance is a growing problem with enteric pathogens worldwide, and Shigella is no exception. Unfortunately, the provincial database did not include resistance profile for all isolates. This information would be very useful to monitor resistance trends, in order to guide the use of empiric antibiotic treatment, either as a self-treatment during travel, or as a treatment upon return. Conclusions In Quebec, travel-related cases of shigellosis represent a large proportion of total infections. Short-term travelers are at risk, as well as young children. The majority of cases occur in the winter months, corresponding to the peak of travel to sunshine destinations. Continuous efforts should be made to encourage all travelers to seek pre-travel care, and to inform primary care practitioners of health risks faced by their patients abroad, even for those going to a resort. Since no vaccine is available, counseling patients on food and water precautions and to carry along a broad-spectrum antibiotic for self-treatment of travelers diarrhea is important. Our results reinforce the importance of explaining clearly to patients that vaccination against some enteric pathogens, eg, hepatitis A or Salmonella typhi, does not provide protection against all enteric infections. Efforts in vaccine development are crucial, in view of the worldwide burden of the disease, the partial protection provided by observing enteric precautions, and the growing resistance to antibiotics. Continuous surveillance is necessary to monitor emerging trends in epidemiological risk factors, and antibiotics susceptibility should be reported more thoroughly in the provincial database. Acknowledgment This study was funded by the Institut national de santé publique du Québec, Québec, Canada. Declaration of Interests S. G. is a member of the Comité consultif québécois sur la santé des voyageurs (Institut national de santé publique du Québec) and has been a member of the Travel Health Capacity Building Working Group (Public Health Agency of Canada) from 2011 to The other authors state they have no conflicts of interest to declare.

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